Ovarian folliculogenesis entails proliferation as well as differentiation of the developing granulosa cell (GC). Although the central role of gonadotropins in this process is well established, the variable fate of follicles afforded comparable gonadotropic stimulation, suggests the existence of additional intraovarian modulatory mechanism(s). Amongst potential novel modulators of GC ontogeny, Somatomedin-C appears uniquely suited to the task, combining replicative and cytodifferentiative properties. Although Sm-C was previously shown to stimulate bovine GC proliferation, the reciprocal nature of proliferation and differentiation precluded demonstration of its cytodifferentiative potential. To overcome this limitation, preliminary studies reported herein made use of rat GCs of limited growth potential in vitro, thereupon revealing that Sm-C is capable of synergizing with FSH in the induction of progesterone biosynthesis and LH receptors. Significantly, this direct cytodifferentiative effect of Sm-C is distinct from its replicative property, and may thus represent a novel biologic effect of this polypeptide. These observations, coupled with the demonstration of GC immunoreactive Sm-C release, suggest the existence of a novel intraovarian autocrine control mechanism, wherein Sm-C may serve as the central signal, and the granulosa cell its site of production, reception, and action. According to this view, Sm-C of GC origin may play an autocrine role at or adjacent to its site of synthesis, interacting with GC "autoreceptors" to amplify or attenuate gonadotropic control of GC ontogeny. To test this hypothesis, in vitro studies are proposed on the role and regulation of GC immunoreactive Sm-C release, the characteristics and regulation of GC Sm-C receptors, as well as the mechanism(s) and site(s) of action of Sm-C in GC differentiation. In these experiments, the role(s) of endogenously produced Sm-C will be deduced from immunoneutralization studies, using a monoclonal antibody to Sm-C. Similarly, the indentity of the receptor mediating the cytodifferentiative effect of SM-C, will be evaluated through selective blockade of Sm-C receptors with an antireceptor monoclone. The long term objectives of this investigation include studies of the in vivo ontogeny of ovarian Sm-C and its receptor, the identification of ovarian Sm-C-producing cells other than the GC, the role of Sm-C in intraovarian paracrine interaction, and its linkage with defined physiologic processes.